Development of Noviomimetics As C-Terminal Hsp90 Inhibitors

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2016 Jan 29

PMID 26819668

Citations 15

Authors

Mercy Anyika

Mason McMullen

Leah K Forsberg

Rick T Dobrowsky

Brian S J Blagg

Affiliations

Soon will be listed here.

Abstract

KU-32 and KU-596 are novobiocin-derived, C-terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar analogues were designed, synthesized, and evaluated in a luciferase reporter assay, which identified compound 37, a benzyl containing noviomimetic, as the most potent inducer of Hsp70.

Citing Articles

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